Anti-migration micropatterned stent coating

ABSTRACT

An endoprosthesis has an expanded state and a contracted state, the endoprosthesis includes a stent having an inner surface defining a lumen, having an outer surface, and defining a plurality of apertures through the outer surface, wherein the apertures are arranged in a micropattern; and a coating (e.g., polymeric coating) attached to the outer surface of the stent. The coating includes a base and a tissue engagement portion including a second surface facing outwardly from the stent, the tissue engagement portion including a structure that defines a plurality of holes extending inwardly from the second surface toward the base. The holes are arranged in a micropattern. When the endoprosthesis is expanded to the expanded state in a lumen defined by a vessel wall, the structure applies a force that may reduce stent migration by creating an interlock between the vessel wall and the endoprosthesis.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of and priority to U.S. ProvisionalApplication No. 61/867,074, filed Aug. 18, 2013, which is incorporatedherein by reference in its entirety, and incorporates by reference thefollowing applications, each in its entirety: U.S. Provisional PatentApplication No. 61/621,219, entitled ANTI-MIGRATION MICROPATTERNED STENTCOATING filed Apr. 6, 2012, U.S. patent application Ser. No. 13/857,998,entitled ANTI-MIGRATION MICROPATTERNED STENT COATING filed Apr. 6, 2013,and U.S. Provisional Patent Application No. 61/798,685, entitledANTI-MIGRATION MICROPATTERNED STENT COATING filed Mar. 15, 2013.

BACKGROUND OF THE DISCLOSURE

A stent is a medical device introduced into a body lumen and is wellknown in the art. A stent may be delivered in an unexpanded state to adesired location in a bodily lumen and then expanded by an internalradial force. Stents, grafts, stent-grafts, vena cava filters,expandable frameworks, and similar implantable medical devices,collectively referred to hereinafter as stents, have included radiallyexpandable endoprostheses, which have been used as intravascularimplants capable of being implanted transluminally.

Esophageal stents have been used to treat patients suffering from arange of malignant and non-malignant diseases. Most commonly, esophagealstents have been associated with the treatment (e.g., palliative) ofesophageal cancers. Esophageal stents have also been used to reducesymptoms resulting from non-esophageal tumors that grow to obstruct theesophagus and to treat benign esophageal disorders, including but notlimited to refractory strictures, fistulas and perforations. In each ofthese cases, esophageal stents may provide mechanical support to theesophageal wall, may maintain luminal patency, and/or may alleviatesymptoms including pain, choking sensations, and severe difficultyswallowing. Because of the structure of the esophagus and conditionssuch as peristalsis, esophageal stents have been prone to stentmigration. When migration occurs, the patient may experience the returnof symptoms and reintervention (e.g., stent repositioning, stentremoval) may be required.

One way to reduce the risk of stent migration has been to expose baremetal portions of the stent to esophageal tissue. The open, braidedstructure of the stent may provide a scaffold that promotes tissueingrowth into the stent. This tissue ingrowth may aid anchoring thestent in place and may reduce the risk of migration.

In some cases, however, tissue ingrowth has been known to lead toreocclusion of the esophagus, for example, in patients receiving a stentto treat malignant growth. In addition, esophageal stents anchored bytissue ingrowth cannot be moved or removed without an invasive procedure(e.g., causing trauma to a patient). To reduce tissue ingrowth, stentshave been covered with a coating (e.g., made of a polymer, etc.) tocreate a physical barrier between the lumen and the esophageal wall.However, in some circumstance, such stents can have an unacceptableoccurrence of migration, as compared to bare metal counterparts.

Some stents are fully degradable and have been designed to be present ina body lumen for a predetermined period of time following delivery anddeployment after which the stent degrades. However, these stents do nothave control over lumen reocclusion built into its design.

Another way to reduce the risk of stent migration has been to use aflared stent (e.g., in the esophagus). However, stents having flares canhave an unacceptable occurrence of migration. Stents have been known toinclude flares (e.g., flared ends), which include many shapes and bothcovered and uncovered varieties. Flares have been used to anchor a stentat an implantation site (e.g., in the esophagus) and have been shown toreduce migration. However, further decreases in migration rates aredesired.

In one or more applications, removable stents are desired, for example,in applications for treating benign disorders. Some applications ofstents include use as a bridge to treatment and less of a palliativemeasure, due in part to improvements in some cancer therapies and othermethods of treating malignant growths. However, efforts to improveremovability have been at odds with at least some measures taken toreduce risk of stent migration. Improved stents that reduce traumaduring stent removal and improve stent adhesion to the body lumen (e.g.,esophageal wall) are desired.

Some fully covered stents have additionally included a secondwoven-metal layer external to the fully covered stent that may allowtissue ingrowth without allowing tissue overgrowth to occlude the bodylumen (e.g., esophagus, etc.). However, the additional scaffolding thatallows for tissue ingrowth may undesirably increase the stent profile.

Improved stents with, for example, improved resistance to migration,improved stent adhesion to the esophageal wall, and/or improvedremovability are desired. Some tracheal stents have incorporated bumpsor other surface features into the stent itself or have included aplurality of surface protrusions on the outer surface of the stent.

Without limiting the scope of the present disclosure, a brief summary ofsome of the claimed embodiments is set forth below. Additional detailsof the summarized embodiments of the present disclosure and/oradditional embodiments of the present disclosure may be found in theDetailed Description of the Disclosure below. A brief abstract of thetechnical disclosure in the specification is also provided. The abstractis not intended to be used for interpreting the scope of the claims.

BRIEF SUMMARY OF THE DISCLOSURE

The present disclosure provides an endoprosthesis where a preferablypolymeric coating has a number of surface features such as protrusionsor holes that are arranged in a micropattern. As used herein, amicropattern may include a regular or irregular array of micro-scalefeatures (e.g., protrusions such as micropillars, voids such as holes).Generally, micro-scale feature means a feature having a dimension (e.g.,length, width, or height) in a range of from about 1 micrometer to about999 micrometers. Herein, unless the context indicates otherwise,micro-scale features are referred to as micropillars (e.g., extendingfrom a base) or holes. In one or more embodiments disclosed herein, abiointeractive micropatterned stent coating may provide a solution formaintaining luminal patency while including potential for removabilityand reducing migration.

Herein, micro-scale features are referred to as micropillars (e.g.,extending from a base) and holes (e.g., microholes, extending within atissue engagement portion). It should be noted that, unless the contextindicates otherwise, the description of micropillar shapes, dimensions,and arrangement applies equally to holes (e.g., microholes).

In at least one embodiment, an endoprosthesis, having an expanded stateand a contracted state, includes a stent with a polymeric coatingattached (e.g., adhered, etc.) to an outer surface of the stent. Thestent has an inner surface defining a lumen. The stent has an outersurface and a stent thickness defined between the inner surface andouter surface. The stent defines a plurality of apertures extendingthrough the stent thickness, wherein the apertures are arranged in amacropattern. In at least one embodiment, the stent is a flared stent.

As used herein, a “macropattern” of apertures (e.g., stent aperatures)refers to a regular or irregular pattern of apertures wherein theshortest center-to-center distance (i.e., the distance between thegeometric centers) of adjacent apertures (i.e., apertures that share aside) is greater than 1000 micrometers. The shortest center-to-centerdistance in a macropattern of stent aperatures is measured when thestent is in a fully expanded state. For example, in a braided stent thatdefines a plurality of four-sided apertures (e.g., extending from aninner surface of the stent to an outer surface of the stent) arranged ina macropattern, the distance between geometric centers of two aperturesthat share one side is greater than 1000 micrometers when the stent isin its expanded state. In a regular pattern of apertures, each of thetwo geometric centers are equidistant from the side shared by theadjacent apertures. In an irregular pattern of apertures, the twogeometric centers are not equidistant from the side shared by theadjacent apertures.

The polymeric coating includes a base and a tissue engagement portion.The base includes a first surface (e.g., attached to the outer surfaceof the stent). The tissue engagement portion includes a second surfacefacing outwardly from the stent (e.g., in a direction opposite of thefirst surface). The tissue engagement portion includes a structure thatdefines a plurality of holes (e.g., microholes, etc.) extending inwardlyfrom the second surface toward the base. In at least one embodiment, theholes are arranged in a micropattern. In one or more embodiments, thebase and the stent are coterminous. In one or more embodiments, the basecovers the apertures of the stent. When the endoprosthesis is expandedto the expanded state in a lumen defined by a vessel wall, the structuredefining the plurality of holes applies a force that creates aninterlock between the vessel wall and the endoprosthesis.

In one or more embodiments, the polymeric coating may include aplurality of protrusions (e.g., micropillars) extending from the base(e.g., outwardly from the stent). In one or more embodiments, theprotrusions may be arranged in a micropattern (e.g., of micropillars).

Although not wishing to be bound by theory, tissue may engage and/orinterlock a micropatterned coating via one or more mechanisms. Forexample, tissue may interlock with a micropatterned coating having oneor more micropillars by growing around and/or between the one or moremicropillars. In at least one embodiment, a tissue ingrowth mechanismmay result in tissue engaging and/or interlocking with a micropatternedcoating having a structure defining one or more holes (e.g., voids,negative spaces, etc.) or networks of connected holes, wherein tissueand/or cell ingrowth occurs within the holes. In one or moreembodiments, a chemical bond mechanism may be formed between a tissue incontact with a micropatterned coating that may include, for example, amucoadhesive gel. In one or more embodiments, engagement of tissue witha micropattern having an appropriate geometry may be by proximityattraction by van der Waals bonding. Herein, “interlock” means to engagetissue (e.g., by a microstructure having micropillars and/or microholes,etc.) via any of the mechanisms (e.g., tissue ingrowth, chemical bond,proximity attraction, etc.) described herein or otherwise known to oneof skill in the art.

The micropattern is specifically designed for a particular tissue inorder to effectively interlock the stent with the tissue. In at leastone embodiment, the micropattern is present along at least a portion ofthe endoprosthesis. In at least one embodiment, the holes of themicropattern can be uniform or the micropattern can be formed of holeshaving a first configuration and holes having at least a secondconfiguration.

The shape of at least some of the plurality of holes may be selectedfrom a group including cylinders, rectangular prisms, polygonal prisms,spheres, spheroids, ellipsoids, and similar shapes. In at least oneembodiment, the holes of the micropattern are cylindrical microholes,each cylindrical microhole having a diameter and a height, wherein thediameter of each cylindrical microhole is equal to its height. In atleast one embodiment, the cylindrical microhole has a lateral surface,wherein the lateral surface of the cylindrical microhole is separatedfrom the lateral surfaces of an adjacent microhole by a distance greaterthan the diameter of the cylindrical microhole. In at least oneembodiment, the micropattern is a grid pattern.

In at least one embodiment, each hole of the micropattern has a firstdimension and a second dimension, wherein the first dimension is betweenabout 1 μm and 999 μm (e.g., between about 1 μm and 100 μm), wherein thesecond dimension is between about 1 μm and 999 μm (e.g., between about 1μm and 100 μm), and wherein each hole is spaced apart from an adjacenthole by a distance (e.g., measured along the second surface), wherein aratio between the distance and the first dimension is between about 2.1and 2.4. In at least one embodiment, each protrusion has a ratio betweenthe first dimension and the second dimension that is between about 1 and1.3.

In at least one embodiment, the endoprosthesis is retrievable by, forexample, a retrieval loop at a distal end of the stent.

Several methods of manufacturing an embodiment of the endoprosthesis areprovided. One method of manufacturing includes forming a polymericcoating, wherein the polymeric coating includes a base and a tissueengagement portion. The base includes a first surface. The tissueengagement portion includes a second surface facing away from the firstsurface and includes a structure that defines a plurality of holesextending inwardly from the second surface toward the base. In one ormore embodiments, the holes are arranged in a micropattern. The methodfurther includes providing a stent having an inner surface defining alumen and an outer surface; and attaching the base of the polymericcoating to the outer surface of the stent.

In one or more embodiments, the micropattern of holes may be made usinglithography techniques, salt leaching, electrospinning, and/or laserablation. In some embodiments that include a micropattern ofmicropillars, the polymeric coating can be formed using a mold having aninverse of the micropattern and injecting a polymeric material into themold and, in some cases applying temperature or pressure to the mold,before the polymeric material cures; using soft lithography techniques,or by etching the polymeric coating from a layer of the polymericmaterial. In at least one embodiment, an adhesive layer is applied to atleast one of a surface of the base and the outer surface of the stent.In at least one embodiment, the polymeric coating is formed as a tubularstructure. In one or more embodiments, the polymeric coating is formedin a strip, which is wrapped (e.g., helically wrapped, circumferentiallywrapped, randomly wrapped, etc.) about the outer surface of the stent.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING(S)

FIG. 1 shows a plan view of an endoprosthesis having a micropattern ofmicrofeatures (e.g., micropillars).

FIG. 2A shows a cross-section of the endoprosthesis shown in FIG. 1.

FIG. 2B is an exemplary enlarged view of the polymeric coating of theendoprosthesis shown in FIG. 1.

FIG. 3A shows a plan view of an endoprosthesis having a polymericcoating having a plurality of holes.

FIG. 3B shows a cross-section of the endoprosthesis shown in FIG. 3A.

FIG. 3C is an exemplary enlarged schematic of a polymeric coating havinga plurality of holes representing the inset of FIG. 3B.

FIG. 3D is an exemplary enlarged schematic of a cross section of thepolymeric coating of FIG. 3C having a plurality of holes representingthe inset of FIG. 3B.

FIGS. 3E-3G are other exemplary enlarged schematics of a cross sectionof the polymeric coating of FIG. 3B (see inset) having a plurality ofholes.

FIG. 4 shows a cross-section of a portion of the polymeric coating shownin FIG. 2B.

FIGS. 5-7 show cross-sections of portions of embodiments of thepolymeric coating.

FIGS. 8A-8J show cross-sections of the micropillars of the polymericcoating shown in FIGS. 2B and 4-6.

FIGS. 9A-9J show plan views of embodiments of the polymeric coatingshown in FIG. 2B.

FIG. 10A shows an embodiment of the polymeric coating of the presentdisclosure.

FIG. 10B shows an embodiment of the polymeric coating of the presentdisclosure.

FIGS. 10C-10F show embodiments of arrays of microfeatures (e.g.,micropillars) forming a micropattern.

FIG. 11 is a view of a stent and polymeric coating during one or moremethods of manufacturing an endoprosthesis.

FIG. 12 is a view of a stent and polymeric coating during one or moremethods of manufacturing an endoprosthesis.

DETAILED DESCRIPTION OF THE DISCLOSURE

While the subject matter of the present disclosure may be embodied inmany different forms, there are described in detail herein specificpreferred embodiments of the present disclosure. This description is anexemplification of the principles of the present disclosure and is notintended to limit the present disclosure to the particular embodimentsillustrated.

For the purposes of this disclosure, like reference numerals in thefigures shall refer to like features unless otherwise indicated.

The present disclosure relates to micropatterned polymeric coatings foruse on medical devices. In some embodiments, the micropatternedpolymeric coatings are utilized with implantable medical devices, suchas stents, to reduce or prevent stent migration, particularly for stentsused in the gastroesophageal system, including, but not limited to,esophageal, biliary, and colonic stents. In one or more embodiments, themicropatterned polymeric coating may include regularly or irregularlyspaced, regularly or irregularly shaped micro-scale holes (e.g., voids,spaces, channels, passages, etc.) that may promote, for example,controlled cell migration and tissue ingrowth. Ingrowth of tissue intothe micropatterned polymeric coatings (e.g., into the holes) may reducestent migration by anchoring the stent to a body lumen wall (e.g., viacontrolled cell ingrowth, etc.). In one or more embodiments, themicropatterned polymeric coating may include and/or be formed from abiodegradable material, which may allow, for example, atraumatic stentremoval in one or more applications. The stents described in thisapplication may be used in the trachea, the cardiovascular system, andelsewhere in the body (e.g., any body lumen).

FIGS. 1 and 2A show an esophageal endoprosthesis 20 of the presentdisclosure with a proximal end 22 and a distal end 24. Theendoprosthesis 20 includes an expandable stent 40 and a polymericcoating 50. Expandable stent 40 can be self-expanding, balloonexpandable, or hybrid expandable. In one or more embodiments, expandablestent 40 is a braided stent that includes a plurality of wires and/orfilaments that collectively form a braided construction. Embodiments ofthe expandable stent 40 contemplate stents having a constant diameter,one or more tapers, one or more flares and/or other changes in diameterin the body and/or at one or more ends. The expandable stent 40 has aninner surface 42, an outer surface 44, a first end 46 and a second end48, and the polymeric coating 50 is disposed about at least a portion ofthe outer surface 44. In at least one embodiment, the polymeric coating50 substantially covers the entire outer surface 44 of the expandablestent 40. In some embodiments, the polymeric coating 50 covers a portionof the outer surface 44 of the expandable stent 40 (e.g., at least 60%,at least 80%, at least 90%, at least 95%, at least 99% of the area ofthe outer surface 44). As shown in FIG. 2A, the polymeric coating 50 canbe directly connected to the outer surface 44 of the expandable stent40. In one or more embodiments, the polymeric coating 50 can beconnected to the outer surface 44 of the expandable stent 40 using anadhesive or other means of attaching the coating to the device. In atleast one embodiment, the polymeric coating at least partially coversthe inner surface 42 also. In at least one embodiment, partial coveragecan include partial coverage of the perimeter and/or the length. In oneor more embodiments, the polymeric coating 50 may be disposed along theentire stent length, may be incorporated into a silicone coating (e.g.,in a patchwork), may be applied to another coating, may be disposed onone or more stent flares, and/or helically wrapped around a body of thestent.

In at least one embodiment, shown in FIGS. 2A and 2B, the polymericcoating 50 includes a base 52 and a plurality of protrusions, such asmicropillars 54, extending outwardly from the base 52. In at least oneembodiment, the micropillars are incorporated (e.g., seamlesslyincorporated, etc.) into the base of the coating. In at least oneembodiment, the base 52 is coterminous with the expandable stent 40.What is meant by “coterminous” is that the base 52 of the polymericcoating 50 and the expandable stent 40 have the same boundaries, coverthe same area, and are the same in extent. In other words, theexpandable stent 40 and the base 52 each have first and second ends, andthe expandable stent 40 and the base 52 extend between their first andsecond ends. The first end of the expandable stent 40 is the same asfirst end of the base 52, and the second end of the expandable stent 40is the same as the second end of the base 52. Since the expandable stent40 and the base 52 extend between their first and second ends, theexpandable stent 40 and the base 52 have the same boundaries, cover thesame area, and are the same in extent. Thus, the base 52 and theexpandable stent 40 are coterminous. The expandable stent 40 and thebase 52 therefore are coterminous in at least one embodiment. Also, base52 is tubular in at least one embodiment.

In at least one embodiment, shown in FIGS. 3A-3G, the polymeric coating50 may include a base 52 and tissue engagement portion 53. Base 52includes a first surface 71 attached (e.g., adhered, bonded, etc.) tothe outer surface of the stent 40 (not shown) in FIGS. 3C-3D. Tissueengagement portion 53 includes a second surface 72 facing outwardly fromthe stent 40. The second surface may define a plurality of openings fromwhich holes 54 h may extend. The tissue engagement portion 53 mayinclude structure 61 defining a plurality of holes 54 h, such as thecylindrical microholes 54 h (FIGS. 3C-3D), extending inwardly from thesecond surface 72 of the tissue engagement portion 53 toward base 52. Inat least one embodiment, the structure 61 is seamlessly incorporatedinto the base 52 of the coating 50. In at least one embodiment, the base52 is coterminous with the expandable stent 40. As shown in FIG. 3C, theholes 54 h are arranged in a micropattern, which may include regularlyshaped holes (e.g., FIGS. 3C, 3E, and 3F) and/or irregularly shapedholes (FIG. 3G), and which may include holes 54 h arranged in a regularpattern (e.g., FIGS. 3C, 3F) and/or in an irregularly micropattern(e.g., FIGS. 3E, 3G). In one or more embodiments, the base 52 covers theapertures of the stent 40 (e.g., FIG. 3A).

In one or more embodiments, the plurality of openings in the secondsurface 72 includes a first opening and a second opening and theplurality of holes includes at least a first hole extending from thefirst opening and a second hole extending from the second opening,wherein the first hole and second hole are in fluid communication via achannel disposed between the first surface and the second surface. Forexample, in FIG. 3E, there is a plurality of holes 54 h that are shownto be located at the second surface 72 and between the second surfaceand the base 52. In FIG. 3E, each of the holes 54 h below the secondsurface 72 is meant to be in fluid communication with at least one hole54 h at the second surface 72 which would allow tissue ingrowth (e.g.,cell migration) from the second surface toward the base 52. FIG. 3Fshows a regular arrangement of a plurality of holes 54 h at and belowthe second surface 72. Similarly, the holes 54 h between the secondsurface 72 and the base 52 are meant to be in fluid communication withat least one hole 54 h at the second surface, such that tissue ingrowthis possible into the holes 54 h. In some embodiments, a network of holesmay be formed wherein cells may invade. A network of holes may be usefulin that the coating may allow for tissue ingrowth while maintaining thestent's relatively low profile (relative to a stent having additionalscaffolding on the outside of the stent for tissue ingrowth and reducingstent migration) while reducing or preventing reocclusion of the lumen.Additionally, structure 61 may be adapted to allow controlled cellingrowth at an implantation site and allow atraumatic removal of thestent (e.g., before, during, and/or after cell ingrowth occurs).

In one or more embodiments, one or more holes 54 h may extend completelythrough the thickness of the coating 50. In one or more embodiments, oneor more of the holes 54 h is a blind hole (e.g., a cavity, anindentation, a hole having a bottom, a hole that does not extend fromthe second surface 72 to the first surface 71. For example, FIGS. 3C-3Ddepict a plurality of holes 54 h that are blind holes. In one or moreembodiments, all of the holes 54 h are blind holes (i.e., no holesextend from the second surface to the first surface).

As shown in FIG. 3G, structure 61 of the tissue engagement portion 53may include a plurality of intertwining fibers, wherein the arrangementof fibers creates a network of holes 54 h between the second surface 72and the base 52. In the present disclosure, the size of a hole 54 h maybe defined by a diameter of the largest sphere that could fit within aparticular three-dimensional space between the second surface 72 and thebase 52.

As may be implied from FIGS. 3A-3G, the first surface 71 may define alength and a width of the coating 50 and the second surface 72 of thecoating 50 may extend around the plurality of holes continuously alongat least one of the length and width of the coating. For example, secondsurface 72, as depicted in FIG. 3C extends continuously around aplurality of holes 54 h along the coating length and width.

In some embodiments as shown in FIGS. 2B and 4-7, the micropillars arecylinders (FIG. 2B), prisms with a rectangular or polygonal base (FIG.4), pyramids (FIG. 5), bumps (FIG. 6), or has a non-traditional shapewith a plurality of bumps and ridges on multiple surfaces that do notdefine a cross-section that is circular, square, polygonal, etc. (FIG.7). Each micropillar can have a circular cross-section (FIG. 8A), squarecross-section (FIG. 8B), rectangular cross-section (FIG. 8C),star-shaped cross-section (FIG. 8D), hexagonal cross-section (FIG. 8E),pentagonal cross-section (FIG. 8F), heptagonal (FIG. 8G), octagonalcross-section (FIG. 8H), nonagonal cross-section (FIG. 8I), decagonalcross-section (FIG. 8J), other polygonal cross-sections, ornon-traditional shaped cross-sections. Each cross-section has a firstdimension h that is the greatest distance between the outer surface ofthe base and the end of the pillar and a second dimension d that is thegreatest distance between two opposite sides (e.g., of the pillar). Forexample, for the circular cross-section the second dimension d is thediameter, for the square d is between two sides, for the rectangle, themajor dimension is between the two shorter sides, for the star, themajor dimension is between two points, for the hexagon the majordimension is between two opposite points. In some embodiments, thesecond dimension d is between midpoints of two opposite sides. In atleast one embodiment, a cross section of the micropillar taken in theradial direction has at least four sides. Embodiments of the presentdisclosure contemplate polygonal cross-sections having all sides ofequal length, combinations of sides of equal length and unequal length,or all sides of unequal length. Embodiments of the present disclosurecontemplate multiple pillars of multiple cross-sectional shapesincluding traditional shapes (e.g. circles, squares, rectangles,hexagons, polygons, etc.) and non-traditional shapes having a perimeterwhere at least a portion of the perimeter is curvilinear. In at leastone embodiment, the micropillars are solid structures, but in otherembodiments they can be hollow structures. In at least one embodiment,each micropillar has a constant cross-section, but in other embodimentsthe micropillars have variable cross-sections. In at least oneembodiment, a micropillar extends perpendicularly from a base (e.g.,FIG. 4). In at least one embodiment, a micropillar extends from a basein a non-perpendicular angle (e.g., FIG. 5) wherein geometric center 57(see, e.g., FIG. 2B) of the end 58 of the micropillar is offsetlaterally from the geometric center of the area of the base covered bythe micropillar (e.g., FIG. 5). In FIG. 5, a longitudinal axis of themicropillar 54 extending through the geometric centers of the lateralcross-sections forms an angle that is less than 90 degrees with base 52.In at least one embodiment, the plurality of micropillars 54 can bearranged in one or more particular micropatterns.

In one or more embodiments, holes 54 h (see FIG. 3C) may take any of theshapes and dimensions (e.g., h, d, s of FIG. 2B) described hereinregarding micropillars 54. For example, holes 54 h may take the shape ofa prism having a cross-section defined by any of the shapes of FIGS.8A-8J. In one or more embodiments the shape of holes 54 h may beselected from a cylinder, a rectangular prism, a prism with a polygonalbase, a sphere, a spheroid, and an ellipsoid. In other examples,structure 61 may define holes 54 h having the same shapes as those shownfor micropillars 54 in FIGS. 4-7. Of course, the height h of the holes54 h may be any height up to and not greater than the thickness of thepolymeric coating 50 (e.g., the sum of thickness of the base 52 and thetissue engagement portion 53). In one or more embodiments, the base iscontinuous and is devoid of holes extending therethrough. In one or moreembodiments, the base 52 includes a base structure that defines aplurality of base holes (e.g., which may be in fluid communication withthe plurality of holes 54 h of the tissue engagement portion 53).

Although not wishing to be bound by theory, the micropattern may affectthe strength of the frictional engagement or interlock between theendoprosthesis and the vessel wall. Likewise, the micropattern isdependent upon the desired frictional engagement or interlock betweenthe microfeatures (e.g., micropillars, holes, etc.) of theendoprosthesis and the tissue. For this reason, in at least oneembodiment, a particular microstructure can be selected that has amicropattern geometry and dimensions suitable for a particularapplication (e.g., implantation site, biological tissue, desired tissueengagement properties, etc.).

Throm Quinlan et al. disclose that “[c]ells such as fibroblasts,endothelial cells, and muscle cells actively sense both the externalloading applied to them (outside-in signaling) and the stiffness oftheir surroundings (inside-out signaling). They respond to these stimuliwith changes in adhesion, proliferation, locomotion, morphology, andsynthetic profile.” See Throm Quinlan et al., “Combining Dynamic Stretchand Tunable Stiffness to Probe Cell Mechanobiology In Vitro,” 2011, PLoSONE 6(8): e23272. Thus, specific structure of micro-scale features(e.g., holes, voids, pores, etc.) as well as coating material propertiesmay be useful in controlling cell behavior.

It should be noted that the surface features of micropillars or holesdescribed herein (e.g., bumps of FIG. 6, bumps and ridges of FIG. 7,etc.) may have one or more micro-scale or nano-scale (e.g., from about 1nanometer to about 999 nanometers) dimensions.

In at least one embodiment, the micropillars in the micropattern allhave the same shape, and in other embodiments, the micropillars vary inshape along the polymeric coating. Thus, in at least one embodiment, themicropattern can include portions where the micropillars have a firstconfiguration and portions where the micropillars have a secondconfiguration. Moreover, embodiments include the polymeric coatinghaving only one micropattern or the polymeric coating having multiplemicropatterns. Thus, the polymeric coating can be tailored to specificstructural characteristics of the body lumen (e.g., a vessel, etc.) anda desired frictional engagement or interlock can be achieved, whileusing a single stent.

Similarly, in one or more embodiments, holes may be configured andarranged in the same manner described herein for micropillars. That is,in at least one embodiment, the holes 54 h in the micropattern may allhave the same shape, and in other embodiments, the holes may vary inshape along the polymeric coating. Thus, in at least one embodiment, themicropattern can include portions where the holes 54 h have a firstconfiguration and portions where the holes 54 h have a secondconfiguration. See, for example FIG. 10F which includes a micropatternhaving a first configuration 80 of holes 54 and a second configuration82 of holes 54′. Moreover, embodiments include the polymeric coatinghaving only one micropattern (e.g., of holes, of micropillars, etc.) orthe polymeric coating having multiple micropatterns (e.g., two or moredifferent micropatterns of holes, two or more micropatterns ofmicropillars, one or more micropattern of holes in combination with oneor more micropatterns of micropillars). Thus, the polymeric coating canbe tailored to specific structural and/or anatomical characteristics ofthe body lumen (e.g., a vessel, etc.) and a desired frictionalengagement or interlock can be achieved, while using a single stent. Inone or more embodiments, a micropattern may include one or more holes incombination with one or more micropillars (e.g., a micropatternincluding a first number of holes alternating with a second number ofmicropillars, etc.). In one or more embodiments, a polymeric coating mayinclude a micropattern of micropillars and a micropattern of holes,wherein the micropatterns may or may not overlap.

In at least one embodiment, the dimension d (e.g., of holes, ofmicropillars, etc.) is between 1 μm and 100 μm. In at least oneembodiment, the dimension d is between about 14 μm and 18 μm. In atleast one embodiment, the dimension d is at least equal to the dimensionh (e.g., of holes, of micropillars, etc.). In at least one embodiment, aratio of h to d is between about 1 and 1.3. In at least one embodiment,two adjacent micropillars are spaced apart by a distance s (shown inFIG. 2B). In at least one embodiment, the ratio of the spacing s to thedimension d is between about 2.1 and 2.4.

In some embodiments, the ends 58 of the protrusions, such asmicropillars 54, that are furthest away from the outer surface of thebase can be shaped to improve tissue attachment. In one or moreembodiments, the ends can be tapered, pointed, rounded, concave, convex,jagged, or frayed. The ends 58 of each protrusion (micropillar 54) caninclude a plurality of pillars on an even smaller scale thanmicropillars 54.

Similarly, in some embodiments, the second surface 72 of the tissueengagement portion can be adapted (e.g., shaped, textured, modified,etc.) to improve tissue attachment. In one or more embodiments, thelateral and/or bottom surfaces of the holes 54 h can be tapered,pointed, rounded, concave, convex, jagged, or frayed. The end 58 of eachhole 54 h may include a plurality of pillars and/or holes on an evensmaller scale than holes 54 h.

In at least one embodiment, the protrusions such as micropillars 54 canalso include features such as smooth surfaces, rough surfaces 55 a (FIG.9A), a plurality of bumps 55 b extending outwardly from a surface of themicropillar (FIG. 9B), a plurality of indentations 55 c extendinginwardly from a surface of the micropillar (FIG. 9C), a plurality ofridges 55 d on a surface of the micropillar (FIG. 9D), a tip 55 e at ornear the end of the protrusion that either softer or more rigid than theremainder of the protrusion (FIG. 9E), a frayed tip 55 f (FIG. 9F), aconvex (e.g., rounded) tip (FIG. 9G), a flared (e.g., flat top) tip(FIG. 9H), a concave (e.g., rounded) tip (FIG. 9I), a tip having a firstdimension dt that is greater than a dimension d of the micropillarcolumn extending between the base 52 and the tip (FIG. 9J), and otherfeatures that may impart useful (e.g., desirable) gripping, stiffness,or flexibility characteristics for the endoprosthesis, and anycombination of features thereof. In at least one embodiment, the tip 55e can include a different material than the remainder of the protrusion.Similarly, the end 58 and lateral surfaces 59 h of holes 54 h may beshaped to improve tissue attachment similar to that described above withrespect to micropillars 54. For example, holes 54 h may include featuressuch as smooth surfaces, rough surfaces, a plurality of bumps extendingoutwardly from a surface of the hole 54 h, a plurality of indentationsextending inwardly from a surface of the hole 54 h, a plurality ofridges on a surface of the hole 54 h, a frayed end 58, a convex (e.g.,rounded) end, a flared (e.g., flat bottom) end, a concave (e.g.,rounded) end, a bottom having a first dimension dt that is greater thana dimension d of a cylindrical column extending between the secondsurface 72 and the end, and other features that may impart useful (e.g.,desirable) gripping, stiffness, or flexibility characteristics for theendoprosthesis, and any combination of features thereof.

FIG. 2B shows an enlarged view of the polymeric coating 50 havingmicropillars. In at least one embodiment, the micropillars are cylindersthat each have a diameter d and a height, h measured from an outersurface 56 of the base 52 to an end 58 (e.g., top surface, etc.) of thecylinder for micropillars. In at least one embodiment, the diameter d isbetween 1 μm and 150 μm (e.g., between 1 μm and 100 μm, between 1 μm and50 μm, between 1 μm and 20 μm, etc.). In at least one embodiment, thediameter d is between about 14 μm and 18 μm. In at least one embodiment,the diameter d of the micropillar is at least equal to its height h. Inat least one embodiment, a ratio of height h of the micropillar 54 tothe diameter d of the micropillar 54 is between about 1 and 1.3. In atleast one embodiment, the micropillars 54 each have a lateral surface59. In at least one embodiment, two adjacent micropillars are spacedapart. The micropillars should be spaced apart enough to encourageengagement and/or interlocking, for example, via an engagement mechanism(e.g., tissue ingrowth, chemical bond, proximity attraction via van derWaals forces, etc.). For tissue ingrowth, for example, the micropillarsshould be spaced apart enough so that the tissue of the bodily vesselcan fill the negative space (e.g., void space) between the pillars. Ifthe spacing is too small, tissue ingrowth may not occur (e.g., thetissue may not be able to actually interlock). In at least oneembodiment, the spacing between the micropillars is dependent upon(e.g., may be selected based upon) the particular type of tissue of thebodily vessel. In at least one embodiment, the spacing s measuredbetween the centers 57 of one micropillar and an adjacent micropillar isgreater than the diameter d of the one micropillar. In at least oneembodiment, the ratio of the spacing s to the diameter d is betweenabout 2.1 and 2.4.

FIG. 3C shows an enlarged view of the polymeric coating 50. In at leastone embodiment, the holes 54 h are cylinders that each have a diameter dand a height, h measured from the second surface 72 of the tissueengagement portion to an end 58 (e.g., bottom surface, etc.) of thecylinder. In at least one embodiment, the diameter d is between 1 μm and150 μm (e.g., between 1 μm and 100 μm, between 1 μm and 50 μm, between 1μm and 20 μm, etc.). In at least one embodiment, the diameter d isbetween about 14 μm and 18 μm. In at least one embodiment, the diameterd of the hole is at least equal to its height h. In at least oneembodiment, a ratio of height h of the hole 54 h to diameter d of thehole is between about 1 and 1.3. In at least one embodiment, the holes54 h each have a lateral surface 59 h. In at least one embodiment, twoadjacent holes 54 h are spaced apart (e.g., spaced apart at the secondsurface 72 of the tissue engagement portion 53). The micropillars shouldbe spaced apart enough to encourage engagement and/or interlocking, forexample, via an engagement mechanism (e.g., tissue ingrowth, chemicalbond, proximity attraction via van der Waals forces, etc.). For tissueingrowth, for example, the holes should be spaced apart enough so thatthe tissue of the bodily vessel can fill the negative space (e.g., voidspace) within the holes. If the spacing between holes is too large,tissue ingrowth may not be able to occur (e.g., the tissue may not beable to actually interlock). In at least one embodiment, the spacingbetween the holes may be is dependent upon (e.g., may be selected basedupon) the particular type of tissue of the bodily vessel. In at leastone embodiment, the spacing s measured between the centers 57 of onehole and an adjacent hole along the second surface 72 is greater thanthe diameter d of the one hole (e.g., greater than the sum of the radiiof the one hole and the adjacent hole). In at least one embodiment, theratio of the spacing s between adjacent holes to the diameter d of theholes is between about 1.01 and 2.0 (e.g., between about 1.01 and 1.5).

In at least one embodiment, the micropillars and/or holes are spacedapart equidistantly in the micropattern. In at least one embodiment, themicropattern of micropillars is a rectangular array (e.g., FIG. 2C, FIG.3C, FIG. 10C). In at least one embodiment, the micropattern is a gridpattern (e.g., a square array as in FIGS. 2C, 3C, 10C, 11). In at leastone embodiment, the micropattern is a regular n-polygonal array (e.g.,hexagonal array in FIGS. 10D, 10E, 10F), wherein a micropillar or holemay be present in the center of the polygon (e.g., FIG. 10C, FIG. 10D,FIG. 10F, etc.) or may not be present in the center of the polygon(e.g., FIG. 10E FIG. 10F). In other words, in the micropattern, themicropillars and/or holes are arranged in rows and columns in themicropattern, wherein the rows and columns may or may not beperpendicular. For example, the micropattern of FIG. 10C includes rowsand columns that are perpendicular, whereas the micropattern of FIGS.10D, 10E, and 10F includes rows and columns that are not perpendicular.In one or more embodiments, each micropillar or hole has a longitudinalaxis and the micropillars are axially aligned in at least one of theaxial direction (e.g., arranged in a row parallel to a longitudinal axisof a stent) and the circumferential direction of the endoprosthesis(e.g., arranged in a row extending circumferentially around alongitudinal axis of a stent). In at least one embodiment, themicropattern of micropillars or holes includes any or all of thefeatures described in this paragraph. In some embodiments, like theembodiments shown in 10A and 10B, the micropattern may cover only aportion of the base 52 rather than the entire base 52. The micropatternof micropillars or holes may be helically disposed on the base 52, asshown in FIG. 10A. In one or more embodiments, as shown in FIG. 10B, afirst micropattern may be disposed longitudinally along the base 52 anda second micropattern is disposed circumferentially about the base sothat the micropattern forms a “window pane”-like configuration. Asdepicted in FIG. 10B, the micropillars arranged in a row (e.g., parallelto a longitudinal axis of a stent) may be continuous rows ordiscontinuous rows (e.g., aligned row segments separated by a gap havinga dimension greater than s), wherein the length of the discontinuity mayhave any length (e.g., 2 or more times the dimension s). For example,the embodiment depicted in FIG. 10B shows discontinuous rows (andcircumferentially oriented columns) extending across the window paneswherein the length of the discontinuity is five times the dimension s(see FIG. 2C) whereas the embodiment depicted in FIG. 10E showsdiscontinuous rows (and nonperpendicularly oriented columns) wherein thelength of the discontinuity is two times the dimension s (see FIG. 2C).In terms of the dimension s shown in FIGS. 2C and 3C, a row and/orcolumn discontinuity may have any length (e.g., at least 2 times s, atleast 5 times s, at least 10 times s, at least 50 times s, at least 100times s, at least 500 times s, at least 1000 times s, etc.). Similarly,any of the micropatterns described herein may include one or more holesinstead of one or more micropillars (e.g., all holes).

Regarding the material used for the polymeric coating 50, it is usefulthat the material be flexible and/or elastic enough to create aneffective interlock with the tissue, be able to withstand the processingfor creating the polymeric coating 50, to accommodate stent mechanicssuch as elongation and conformability to tortuous anatomy. Examples ofacceptable materials include, but are not limited to, flexiblesilicones, hydrogels, mucoadhesive substrate, pressure-sensitiveadhesives, and other suitable elastomers, such as synthetic rubbers. Inone or more embodiments, a coating having a micropattern may includeand/or be formed from a biologically-derived protein structure (e.g.,collagen, etc.). Other acceptable materials include any flexible,biocompatible, and non-biodegradable polymer. For palliative treatmentstent applications, it may be useful for the coating to include one ormore non-biodegradable polymers and/or a material having a degradationprofile that may be useful for the particular stent application andimplantation site. In one or more embodiments, the coating may bebiodegradable in order to, for example, allow stent removal (e.g., aftersome portion or all of the coating has degraded). Applications in whichit may be useful to remove a stent include support during perforationhealing, dilatation of benign structures, and bridge to surgery.

In at least one embodiment, the polymeric coating 50 (e.g., havingmicropillars 54 and/or holes 54 h) may include proteins capable ofengaging and/or interlocking with the tissue wall in a biochemicalmanner. In one or more embodiments, the polymeric coating 50 may include(e.g., be laced with) one or more growth factors that promote cellmigration and/or control the amount and timing of cell invasion/tissueingrowth between micropillars and/or within holes. In at least oneembodiment, the polymeric coating 50 may include at least onetherapeutic agent. In other embodiments, an additional coating may beapplied to the polymeric coating 50 that includes a therapeutic agent. Atherapeutic agent may be a drug or other pharmaceutical product such asnon-genetic agents, genetic agents, cellular material, etc. Someexamples of suitable non-genetic therapeutic agents include but are notlimited to: anti-thrombogenic agents such as heparin, heparinderivatives, vascular cell growth promoters, growth factor inhibitors,paclitaxel, etc. Where an agent includes a genetic therapeutic agent,such a genetic agent may include but is not limited to: DNA, RNA andtheir respective derivatives and/or components. Where a therapeuticagent includes cellular material, the cellular material may include butis not limited to: cells of human origin and/or non-human origin as wellas their respective components and/or derivatives thereof. In one ormore embodiments, a suitable therapeutic agent (e.g., small organicmolecules, peptides, oligopeptides, proteins (e.g., “hedgehog” proteins,etc.), nucleic acids, oligonucleotides, genetic therapeutic agents,non-genetic therapeutic agents, vectors for delivery of genetictherapeutic agents, cells, therapeutic agents identified as candidatesfor vascular treatment regimens, etc.) may include any one or more ofthose disclosed in U.S. Pat. No. 8,267,992 (Atanasoska et al.), which isincorporated by reference herein in its entirety. In one or moreembodiments, one or more therapeutic agents may be included within or onpolymeric coating 50, including the micropillars 54 and/or holes 54 h.

In one or more embodiments, the base 52 may be formed from the samematerial as the micropillars 54 and/or the structure 61 of the tissueengagement portion 53. In one or more embodiments, the micropillars 54and/or structure 61 are formed from one material and the base 52 isformed from a different material. In one or more embodiments, themicropillars 54 and/or structure 61 are formed with layers of material,and these layers can be the same material or can be different materialsdepending on the characteristics required for the desired frictionalengagement of the endoprosthesis with the vessel wall.

Because the endoprosthesis 20 has improved frictional engagement withthe tissue wall when inserted into a lumen of the patient, removal ofthe stent may be more difficult with some traditional removaltechniques. In at least one embodiment, shown in FIG. 1, theendoprosthesis 20 is provided with a suture or removal loop 55 on oneend of the stent. In at least one embodiment, the removal loop 55 isprovided on a distal end of the stent. It should be noted thatreferences herein to the term “distal” are to a direction away from anoperator of the devices of the present disclosure, while references tothe term “proximal” are to a direction toward the operator of thedevices of the present disclosure. While sutures or removal loops arewell known in the art for removing endoprosthesis, sutures or removalloops have been provided on the proximal end of the stent, in otherwords the closest end to the practitioner. Here, the suture or removalloop is applied to the opposite end of the endoprosthesis. In at leastone embodiment, the practitioner grabs the loop from inside theendoprosthesis, and by applying an axial force to the loop, the distalend of the endoprosthesis is pulled through the lumen of theendoprosthesis itself. Thus, the micropillars are peeled away from thevessel wall while the stent is flipped inside out to remove theendoprosthesis. In other embodiments, the practitioner may grab the loopfrom outside the endoprosthesis or at an end of the endoprosthesis.Although not shown in FIG. 3A, a suture or removal loop 55 may beprovided on one end of the stent of FIG. 3A.

To manufacture the endoprosthesis 20, several methods can be employed.The polymeric coating 50 can be formed (e.g., molded) separately fromthe stent (e.g., as a polymeric film, a hydrogel film, a thin fibrousnetwork, etc.) and then adhered to the stent (e.g., an outer surface ofthe stent) with an optional adhesive layer 60 disposed between the outersurface of the stent and the base (e.g., the first surface) of thepolymeric coating (e.g., applied to at least a portion of one or both ofthe first surface of the base and the outer surface of the stent).Polymeric material can be injected into a mold with the inverse of themicropattern to create the polymeric coating having a micropattern ofmicrofeatures (e.g., micropillars, holes, etc.). Also, the polymericmaterial can be pulled through a mold using a vacuum pump system. In atleast one embodiment, the polymeric coating can be created using softlithography techniques. In one or more embodiments, etching techniquescan be used to create the coating, wherein material is taken away from alayer of the coating material to create the micropattern of thepolymeric coating 50. In yet another embodiment, a technique called hotembossing can be used, which involves stamping partially cured polymerinto the desired shape of the polymeric coating and then curing itbefore it is applied to the stent. Stamping may or may not include theuse of a solvent. In one or more embodiments, a stent may be coated byany suitable method (e.g., spraying, dipping, injection molded, etc.),followed by the introduction of holes into the coating after the stentcoating. In some embodiments, a fibrous network with micro-scale holes(e.g., voids) may be formed by electrospinning one or more fibers on apre-coated stent. In one or more embodiments, a laser ablation processmay be used (e.g., using one or more appropriately sized laser beams(e.g., same or different sizes depending on the desired pattern) toremove material from a coating in order to form one or more micropillarsand/or one or more microholes.

In one or more embodiments, one or more portions of coating may bedeployed into a body lumen separately from a stent (e.g., as one or morepads, etc.). Then, for example, a pressure-sensitive adhesive may beapplied to an applicable portion of a stent meant to attach to thepre-deployed coating (e.g., biointeractive pads). The radial expansiveforce of the stent during and after deployment may activate the adhesiveand adhere the stent to the coating previously deployed in a body lumen.

In one or more embodiments, a polymeric coating 50 having holes (e.g.,microholes) may be formed by using a technique called particulateleaching (e.g., salt leaching), wherein a composite material is formedfrom one or more polymeric materials and one or more particulates (e.g.,salts), followed by leaching the one or more particulates (e.g., salts)from the composite material (e.g., with a solvent) resulting in acomposite and/or polymeric material having holes or voids where the oneor more particulates (e.g., salts) were removed. In one or moreembodiments, a polymeric coating having a plurality of holes may beformed by a technique called electrospinning (e.g., using an electricalcharge to draw very fine fibers from a liquid), wherein the polymericcoating includes a plurality of fibers arranged at or near the baseforming holes (e.g., a network of holes, a network of voids) between thefibers. In one or more embodiments, the use of salt leaching and/orelectrospinning provides a polymeric coating 50 having one or more holes54 h that form a network of holes (e.g., a plurality of holes in fluidcommunication below the base). In some embodiments, cell ingrowth may beenhanced when the polymeric coating includes a network of holes. In oneor more embodiments, any of a wide variety of therapeutic agents (e.g.,growth factors) including, but not limited to, those described hereinmay be included on, within, and/or in combination with a network ofholes to promote tissue ingrowth when the micropatterned polymericcoating contacts tissue.

In at least one embodiment, as shown in FIG. 11, the coating 50 can bemolded as a substantially tubular structure with a lumen defined by thebase of the coating. An adhesive layer 60 can be applied to either thestent or to at least a portion of the inner surface of the base of thecoating. In at least one embodiment, the adhesive layer 60 maysubstantially cover the entire inner surface of the base of the coating.The stent 40 can be inserted into the lumen of the coating 50. In atleast one embodiment, heat and/or pressure may be applied to ensureproper adhesion of the coating 50 to the stent 40 via the adhesive layer60. The adhesive layer may include silicone coatings, other suitableadhesives, or priming solutions that enable the coating to adhere to themetal stent (or stent coating thereon). In one or more embodiments, asshown in FIG. 12, rather than being molded as a tubular structure, thecoating 50 can be molded as a strip attached to the outer surface 44 ofthe stent 40. In some embodiments, the strip can be applied as perimeterstrips attached circumferentially about at least a portion of thecircumferential perimeter of the stent. In some embodiments, the stripcan be a longitudinal strip attached to the stent in a longitudinaldirection. In some embodiments, the stent can be helically wrapped aboutthe stent, as shown in FIG. 12. In some embodiments the coating may beapplied as a single strip or as multiple strips. Where the coating isapplied as multiple strips, directly adjacent strips may abut oneanother or may be spaced apart from one another. In at least oneembodiment, the strips may be partial tubular structures that extendalong the length of the stent but only cover a portion of thecircumference of the stent. In some embodiments, a portion of stent 40may be exposed. An adhesive layer 60 can be applied to either the stentor to at least a portion of the base of the coating. In at least oneembodiment, heat and/or pressure may be applied to ensure properadhesion of the coating 50 to the stent 40 via the adhesive layer 60. Inat least one embodiment, discrete micropatterns of micropillars can beformed on and/or attached directly to either the stent 40 or thepolymeric coating 50.

In one or more embodiments, the polymeric coating 50 can be formed bydip-coating the stent 40 in the coating material without needing anadditional adhesive layer to connect the coating 50 to the stent 40. Forexample, the stent 40 can be inserted into a mold, which includes acavity and a tubular member. The cavity is defined by an inner wall ofmold, which is an inverse of the desired micropattern. The stent 40rests on the tubular member such that the inner surface of the stent isdisposed about the tubular member. The mold with the stent 40 can bedipped into the coating material so that the coating material fills themold and attaches to the stent 40. In some embodiments, temperaturechanges and/or pressure changes may be applied to the mold to cure thecoating material. Once the coating material cures to form the polymericcoating 50, the endoprosthesis 20 can be removed from the mold.Alternatively, the polymeric coating 50 can be injection molded onto thestent using a similar mold. The coating material is injected into themold rather than the mold being dipped into the coating material.

A description of some exemplary embodiments of the present disclosure iscontained in the following numbered statements:

Statement 1. An endoprosthesis having an expanded state and anunexpanded state, the endoprosthesis comprising:

a stent, wherein the stent has an inner surface defining a lumen, anouter surface, a first end, a second end, and a stent thickness definedbetween the inner surface and the outer surface, wherein the stentdefines a plurality of apertures extending through the stent thickness,wherein the apertures are arranged in a macropattern; and

a polymeric coating attached to the outer surface of the stent, thepolymeric coating comprising

-   -   a base comprising a first surface attached to the outer surface        of the stent; and    -   a tissue engagement portion comprising a second surface facing        outwardly from the stent, the tissue engagement portion        comprises a structure that defines a plurality of holes        extending inwardly from the second surface toward the base,        wherein the holes are arranged in a micropattern, wherein the        base and the stent are coterminous, wherein the base covers the        apertures of the stent.

Statement 2. The endoprosthesis of statement 1, wherein when theendoprosthesis expands in a lumen defined by a vessel wall, thestructure defining a plurality of holes arranged in a micropatternapplies a force that creates a desired interlock between the vessel walland the endoprosthesis.

Statement 3. The endoprosthesis of statement 1 or statement 2, whereinshape of the plurality of holes is selected from the group consisting ofa cylinder, a rectangular prism, a prism with a polygonal base, asphere, and an ellipsoid.

Statement 4. The endoprosthesis of any of statements 1-3, wherein theplurality of holes of the micropattern are cylindrical microholes, eachcylindrical microhole having a diameter and a height.

Statement 5. The endoprosthesis of statement 4, wherein the diameter isbetween about 1 μm and 100 μm.

Statement 6. The endoprosthesis of statement 5, wherein the diameter isbetween about 14 μm and 18 μm.

Statement 7. The endoprosthesis of statement 4, wherein the height isbetween about 1 μm and 100 μm.

Statement 8. The endoprosthesis of statement 7, wherein the height isbetween about 14 μm and 18 μm.

Statement 9. The endoprosthesis of statement 4, wherein the diameter ofthe cylindrical microhole is equal to the height of the cylindricalmicrohole.

Statement 10. The endoprosthesis of statement 4, wherein eachcylindrical microhole has a lateral surface, wherein the lateral surfaceof the cylindrical microhole is separated from the lateral surfaces ofan adjacent microhole by a distance greater than the diameter of thecylindrical microhole.

Statement 11. The endoprosthesis of statement 1, wherein each hole ofthe micropattern has a first dimension and a second dimension, whereinthe first dimension is between about 1 μm and 100 μm, wherein the seconddimension is between about 1 μm and 100 μm, and wherein a ratio betweenthe first dimension and the second dimension is between about 1 and 1.3.

Statement 12. The endoprosthesis of any of statements 1-11, wherein themicropattern is a grid pattern.

Statement 13. The endoprosthesis of any of statements 1-12, wherein thepolymeric coating is a polymeric material selected from the groupconsisting of hydrogels and silicones.

Statement 14. The endoprosthesis of any of statements 1-13, wherein theholes of the micropattern are uniform.

Statement 15. The endoprosthesis of any of statements 1-14, wherein themicropattern includes holes of a first configuration and holes of atleast a second configuration.

Statement 16. The endoprosthesis of any of statements 1-15, wherein thesecond surface defines a plurality of openings from which the holesextend.

Statement 17. The endoprosthesis of statement 16 wherein the pluralityof openings comprises a first opening and a second opening and theplurality of holes comprises at least a first hole extending from thefirst opening and a second hole extending from the second opening,wherein the first hole and second hole are in fluid communication via achannel disposed between the first surface and the second surface.

Statement 18. The endoprosthesis of any of statements 1-17, wherein thestructure comprises a plurality of intertwining fibers.

Statement 19. The endoprosthesis of any of statements 1-18, wherein thestructure is adapted to allow controlled cell ingrowth at animplantation site and allow atraumatic endoprosthesis removal from theimplantation site after cell ingrowth occurs.

Statement 20. The endoprosthesis of any of statements 1-19, wherein thefirst surface defines a length and a width of the coating and whereinthe second surface of the coating extends around the plurality of holescontinuously along at least one of the length and width of the coating.

Statement 21. A method of manufacturing an endoprosthesis comprising:

forming a polymeric coating, wherein the polymeric coating comprises

-   -   a base comprising a first surface; and    -   a tissue engagement portion comprising a second surface facing        away from the first surface, the tissue engagement portion        comprises a structure that defines a plurality of holes        extending inwardly from the second surface toward the base,        wherein the holes are arranged in a micropattern; and

attaching the base of the polymeric coating to an outer surface of astent, the stent comprising an inner surface defining a lumen.

Statement 22. The method of statement 21, wherein the polymeric coatingis formed using a mold having an inverse of the micropattern andinjecting a polymeric material into the mold.

Statement 23. The method of statement 21 or statement 22, whereinattaching the base of the polymeric coating to the outer surface of thestent comprises applying an adhesive layer to at least one of the firstsurface of the base and the outer surface of the stent.

Statement 24. The method of any of statements 21-23, wherein thepolymeric coating is formed in a strip and helically wrapped about theouter surface of the stent.

The above disclosure is intended to be illustrative and not exhaustive.This description will suggest many variations and alternatives to one ofordinary skill in this art. All these alternatives and variations areintended to be included within the scope of the claims where the term“comprising” means “including, but not limited to.” Those familiar withthe art may recognize other equivalents to the specific embodimentsdescribed herein which equivalents are also intended to be encompassedby the claims.

Further, the particular features presented in the dependent claims canbe combined with each other in other manners within the scope of thepresent disclosure such that the present disclosure should be recognizedas also specifically directed to other embodiments having any otherpossible combination of the features of the dependent claims.

This completes the description of the preferred and alternateembodiments of the present disclosure. Those skilled in the art mayrecognize other equivalents to the specific embodiment described hereinwhich equivalents are intended to be encompassed by the claims attachedhereto.

The invention claimed is:
 1. An endoprosthesis having an expanded stateand an unexpanded state, the endoprosthesis comprising: a stent, whereinthe stent has an inner surface defining a lumen, an outer surface, afirst end, a second end, and a stent thickness defined between the innersurface and the outer surface, wherein the stent defines a plurality ofapertures extending through the stent thickness, wherein the aperturesare arranged in a macropattern; and a polymeric coating attached to theouter surface of the stent, the polymeric coating comprising a basecomprising a first surface attached to the outer surface of the stent;and a tissue engagement portion comprising a second surface facingoutwardly from the stent, the tissue engagement portion comprises astructure that defines a plurality of holes extending inwardly from thesecond surface toward the base, wherein the holes are arranged in amicropattern, wherein the base and the stent are coterminous, whereinthe base covers the apertures of the stent.
 2. The endoprosthesis ofclaim 1, wherein when the endoprosthesis expands in a lumen defined by avessel wall, the structure defining a plurality of holes arranged in amicropattern applies a force that creates a desired interlock betweenthe vessel wall and the endoprosthesis.
 3. The endoprosthesis of claim1, wherein shape of the plurality of holes is selected from the groupconsisting of a cylinder, a rectangular prism, a prism with a polygonalbase, a sphere, and an ellipsoid.
 4. The endoprosthesis of claim 3,wherein the plurality of holes of the micropattern are cylindricalmicroholes, each cylindrical microhole having a diameter and a height.5. The endoprosthesis of claim 4, wherein the diameter of thecylindrical micro hole is equal to the height of the cylindrical microhole.
 6. The endoprosthesis of claim 4, wherein each cylindricalmicrohole has a lateral surface, wherein the lateral surface of thecylindrical micro hole is separated from the lateral surfaces of anadjacent microhole by a distance greater than the diameter of thecylindrical microhole.
 7. The endoprosthesis of claim 1, wherein eachhole of the micropattern has a first dimension and a second dimension,wherein the first dimension is between about 1 μm and 100 μm, whereinthe second dimension is between about 1 μm and 100 μm, and wherein aratio between the first dimension and the second dimension is betweenabout 1 and 1.3.
 8. The endoprosthesis of claim 1, wherein themicropattern is a grid pattern.
 9. The endoprosthesis of claim 1,wherein the polymeric coating is a polymeric material selected from thegroup consisting of hydro gels and silicones.
 10. The endoprosthesis ofclaim 1, wherein the holes of the micropattern are uniform.
 11. Theendoprosthesis of claim 1, wherein the micropattern includes holeshaving a first configuration and holes having at least a secondconfiguration.
 12. The endoprosthesis of claim 1, wherein the secondsurface defines a plurality of openings from which the holes extend. 13.The endoprosthesis of claim 12, wherein the plurality of openingscomprises a first opening and a second opening and the plurality ofholes comprises at least a first hole extending from the first openingand a second hole extending from the second opening, wherein the firsthole and second hole are in fluid communication via a channel disposedbetween the first surface and the second surface.
 14. The endoprosthesisof claim 1, wherein the structure comprises a plurality of intertwiningfibers.
 15. The endoprosthesis of claim 1, wherein the structure isadapted to allow controlled cell ingrowth at an implantation site andallow atraumatic endoprosthesis removal from the implantation site aftercell ingrowth occurs.
 16. The endoprosthesis of claim 1, wherein thefirst surface defines a length and a width of the coating and whereinthe second surface of the coating extends around the plurality of holescontinuously along at least one of the length and width of the coating.